Faculty of Science, Department of Biochemistry, Mahidol University, Bangkok, Thailand.
Graduate Program in Molecular Medicine, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand.
Adv Exp Med Biol. 2021;1286:15-48. doi: 10.1007/978-3-030-55035-6_2.
Several studies have exploited the metabolic hallmarks that distinguish between normal and cancer cells, aiming at identifying specific targets of anti-cancer drugs. It has become apparent that metabolic flexibility allows cancer cells to survive during high anabolic demand or the depletion of nutrients and oxygen. Cancers can reprogram their metabolism to the microenvironments by increasing aerobic glycolysis to maximize ATP production, increasing glutaminolysis and anabolic pathways to support bioenergetic and biosynthetic demand during rapid proliferation. The increased key regulatory enzymes that support the relevant pathways allow us to design small molecules which can specifically block activities of these enzymes, preventing growth and metastasis of tumors. In this review, we discuss metabolic adaptation in cancers and highlight the crucial metabolic enzymes involved, specifically those involved in aerobic glycolysis, glutaminolysis, de novo fatty acid synthesis, and bioenergetic pathways. Furthermore, we also review the success and the pitfalls of the current anti-cancer drugs which have been applied in pre-clinical and clinical studies.
已有多项研究利用正常细胞和癌细胞之间的代谢特征差异，旨在鉴定抗癌药物的特定靶点。很明显，代谢灵活性使癌细胞能够在高合成代谢需求或营养物质和氧气耗尽的情况下存活。癌细胞可以通过增加有氧糖酵解来最大限度地提高 ATP 产生，增加谷氨酰胺分解和合成代谢途径，以在快速增殖期间支持生物能量和生物合成需求，从而使代谢重新编程适应微环境。增加支持相关途径的关键调节酶使我们能够设计小分子，这些小分子可以特异性地阻断这些酶的活性，从而阻止肿瘤的生长和转移。在这篇综述中，我们讨论了癌症中的代谢适应，并强调了涉及的关键代谢酶，特别是参与有氧糖酵解、谷氨酰胺分解、从头脂肪酸合成和生物能量途径的酶。此外，我们还回顾了目前已应用于临床前和临床研究的抗癌药物的成功和缺陷。
